Diarrhoea-predominant IBS is a condition known to arise from non-obvious causes. In particular, Irritable Bowel Syndrome which is defined as being a non-inflammatory bowel disease is known not to be caused by any detectable infection by a pathogenic organism or organisms.
Irritable Bowel Syndrome is therefore not a form of Inflammatory Bowel Disease. Inflammatory Bowel Diseases are characterised by inflammation on histology and inflammation on colonoscopy whereas Irritable Bowel Syndrome shows no evidence of inflammation on colonoscopy and the histology shows no increase in inflammatory cells. Irritable Bowel Syndrome is therefore referred to as a “non specific” bowel disorder because there is no specific diagnostic criterion such as histology or a blood test that can diagnose it. Irritable Bowel Syndrome is only diagnosed when one excludes the presence of other “specific” diseases or disorders such as Salmonella, Gastroenteritis, Campylobacter gastroenteritis, Clostridium difficile infection, Giardiasis, Crohn's disease or Ulcerative colitis. Irritable Bowel Syndrome can be distinguished from infective and inflammatory bowel diseases such as colitis or Crohn's disease on culture or histological grounds and endoscopic appearances.
Irritable Bowel Syndrome is therefore a collection of symptoms such as bloating, diarrhoea, cramping, flatulence, or constipation where there is no specific diagnostic test that turns it into a specific bowel disorder. Irritable Bowel Syndrome may therefore be diagnosed by exclusion of other specific bowel disorders. Another example of a non specific gastrointestinal disorder is non ulcer dyspepsia.
The large bowel in man and to a lesser extent the small bowel, contain large concentrations of various enteric bacteria. Generally, patients will have no pain, cramping, diarrhoea or constipation if the bacterial contents are not infected with pathogenic strains which may colonise the bowel and remain there for prolonged periods of time. Acute infections and some chronic infections of the bowel flora however can cause inflammatory changes in the lining. When inflammation is visible this condition is called Inflammatory Bowel Disease (IBD), which can be transient or long term—for example ‘ulcerative colitis’. In some forms of IBD the visible inflammation is absent and can only be detected by taking a biopsy and finding histological changes of inflammation. In this case the pathologist terms the IBD as “microscopic colitis”.
Where there are no visible colonoscopic or histological abnormalities in the colon and when the stool tests are negative for any known infection, and yet the patient complains of symptoms referrable to the colon, such as urgency, diarrhoea, flatulence, cramping—the diagnosis of Irritable Bowel Syndrome can be made. Between 5% and 25% of the western population in different age groups may suffer from this disorder which has also been termed spastic colon, unstable colonic neurosis, spastic colitis or mucous colitis. In a classic case there is a triad of symptoms including low abdominal pain relieved by defecation, alternating constipation/diarrhoea and the passage of small calibre stools. In some patients there may be accompanying watery diarrhoea with or without pain. Distension, flatulence, wind and at times nausea and headaches may also be accompanying systemic symptoms. At times diarrhoea alternates with constipation.
The pathogenesis of IBS is unclear. Emotional disturbances, fibre deficiency, purgative abuse and food intolerance have been some of the implicated aetiological agents but none have been proven nor well demonstrated. Evidence is therefore lacking for an infective cause or auto-immunity. Conventional treatments for IBS have been unsatisfactory as exemplified by the large number of therapies that have from time to time been recommended or trialed. These have included psychotherapy, dietary regimens, anti-spasm agents, anti-cholinergics, anti-depressants, bulking agents, various receptor antagonists, carminatives, opiates, and tranquillisers—all without substantial success. Indeed there is no evidence that cure is possible. Yet IBS is one of the most common of all the gastrointestinal illnesses and though not life-threatening, causes great distress especially to those severely affected, and may bring a feeling of frustration and helplessness, being generally lifelong. In particular, diarrhoea-predominant IBS can cause incontinence in some patients and, for example, the inability of being sure that one can reach ones employment causing some to drive from rest room to rest room on their way to work. In some patients urgency is so severe that they can only hold their motions for a few seconds.
One treatment that has been proposed for the treatment of IBS and for other bowel diseases is the use of certain classes of aminosalicylic acids. For example Borody in U.S. Pat. No. 5,519,014 describes the use of 5-aminosalicylic acids (5-ASA compounds) for the treatment of IBS. Similarly, Lin et al (U.S. Pat. No. 6,326,364) teaches that 5-ASA compounds can inhibit clostridia (a pathogen).
Whilst prior art methods go some way to treating IBS, there is a need for other treatment regimes and in particular treatment regimes for non-specific bowel disorders such as diarrhoea-predominant IBS which may not be effectively treated by prior art methods.